Bajiaolian, one of the species in the Mayapple family (Podophyllum pelatum), has been widely used as a traditional Chinese herbal medicine for the remedies of snake bites, general weakness, poisons, condyloma accuminata, lymphadenopathy, and certain tumors in China. In Western medicine, Podophyllum was first used medically as a laxative in the early 19th century. Since 1940, the resin of podophyllum has also been used topically for various skin lesions, such as warts and condyloma. Human poisonings have been reported. An animal model was established to investigate the neurotoxic effects of Bajiaolian. Podophyllotoxin, the major active ingredient in Podophyllum, was injected (ip) to young adult male rats at doses of 0, 5, 10, or 15 mg.kg-1 b.w.. The animals were sacrificed 72 h after injection. Neuronal changes were readily observable in animals treated with 10 or 15 mg.kg-1 of the toxin. Edematous changes of the anterior horn motoneurons were observed in the spinal cord. No neuronal necrosis was found. The type of neuronal swelling is believed to be only a transient change and would probably subside with time if no further assaults occur. More serious and perhaps longer term of changes were found in the dorsal ganglion neurons and the nerve fibers (axons) in the central and peripheral nervous system. Severe depletion of the Nissl substance (RNA/polyribosomes) was observed in the dorsal root ganglion neurons. Alterations in these sensory neurons would give rise to and correlate with the sensory disturbances experienced by the patients. Bodian staining also revealed a dose-related increase in the coarseness (thickness) of the nerve fibers (axons) in the cerebellum, cerebral cortex, brainstem, and spinal cord. This is the first scientific study showing the neurotoxicity of Bajiaolian, a commonly used Chinese herbal medicine. Toxicities on other organ systems by this drug certainly exist. Caution should be exercised in the dispensing and usage of this medicine.